Bioequivalence and Bioavailability Forum

Hi Helmut,

Thanks for your reply! I am very familiar with setting up BE studies and thus taking into account CV_intra, but struggling a bit with the "brilliant" idea of my boss for this product regarding CV_inter.

❝ CVs of the product? Do you have data of a replicate study?

We do not have data of a replicate study, but the CV_intra reported in BE studies with IR tablets is about 10-15%. I should have said "CV_intra of the compound when formulated in an IR tablet."

❝ Hhm, why CV_inter?

I should have provided a bit more background. I will try to explain the rationale

The IR tablets currently on the market show low CV_intra, but high differences in terms of bioavailability (AUC) between subjects. Bioavailability after oral administration of IR tablets varies between about 30 to 95%. If a patient shows low BA (low-responder), he/she is switched to injections.

We are developing MR tablets/capsules (eiter EC or CR) which we believe may increase bioavailability for those who show low bioavailability with IR tablets (however, this idea may be far-fetched). If we would be able to raise bioavailability to about 60 to 95% in general, we would have proof of our concept. In other words, more patients would be able to stay on tablets (instead of injections).

❝ ❝ What sample size would be appropriate?

❝

❝ Define appropriate.

Well, this is where I am having doubts. How large should the sample size be to show a potential difference in AUCs between subjects? In other words, how many patients do we need to show that bioavailability is increased from 30-95% with IR tablets to, say, about 50/60-95% with our formulation?

As a consequence, we will obviously not aim for BE and probably end up in a phase III study...

I know that this is kind of a long-shot, but we (read: my boss) are willing to give it a try...

Thanks!